PROJECT SUMMARY Colorectal cancer (CRC) accounts for 8% of cancer incidence and 8% of cancer-related mortality in the United States. While CRC risk and CRC-related mortality overall have decreased in recent years, the proportion of CRC cases among adults ages <50?known as young onset colorectal cancer (YCRC)?has increased. One clinical strategy recommended to detect YCRC earlier is colonoscopy for adults presenting with conditions that might increase YCRC risk, such as iron deficiency anemia (IDA) or hematochezia (visible blood in stool). Colonoscopy in these cases is conducted rule out CRC and has been proven to be particularly effective among elderly adults. However, little evidence exists about the relative benefit among adults ages <50. In light of increased YCRC incidence, a second clinical strategy recommended by the American Cancer Society involves lowering the age of CRC screening initiation from 50 to 45, despite a paucity of evidence that early screening initiation improves CRC-related outcomes in adults ages <50. While previous guidelines advised CRC screening prior to age 50 only among adults with reported family history of CRC, this represents only 30% of all CRC cases, meaning that identification of adults ages <50 most likely to benefit from YCRC- related colonoscopy remains unclear. Furthermore, there are no imminent RCTs offering interventions like colonoscopy for work-up of CRC-related conditions or screening asymptomatic adults, highlighting an urgent need to learn about YCRC-related colonoscopy benefit among adults ages <50. Our study will use national electronic health records and claims-based data from the Veterans Affairs (VA) Corporate Data Warehouse (CDW) to address key gaps in the literature by evaluating these two clinical strategies for colonoscopy uptake to address YCRC incidence and mortality. First, we will examine the benefits of colonoscopy uptake among Veterans ages <50 with conditions (IDA or hematochezia) that may increase CRC risk by comparing CRC risk among adults exposed to IDA or hematochezia (Aim 1a), examining proportion of timely colonoscopy uptake ?60 days of IDA or hematochezia identification (Aim 1b), and comparing YCRC incidence, stage at detection and mortality by colonoscopy uptake among Veterans with IDA or hematochezia (Aim 1c). Next, we will compare the impact of exposure to colonoscopy on YCRC benefits among all Veterans ages 18-49 (Aim 2). Our study will be the most comprehensive examination of early exposure to colonoscopy in the US to date and will have important implications on current clinical guidelines and contextualize current CRC screening policy. Major strengths include: (1) use of EHR and claims-based data from the largest integrated healthcare system in the US; (2) VA studies have played critical roles in US clinical practice changes; and (3) the largest assessment of colonoscopy uptake among adults ages <50 to date. Finally, this study offers a high-quality postdoctoral training opportunity to understand current methods of CRC detection using colonoscopy, and to develop key skills in cancer epidemiology and biostatistics to become a qualified independent investigator.